A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With ST Segment Elevation Myocardial Infarction (STEMI)
Strategic Partnership III Track A
$9 348 792
The proposed project is to conduct a Phase IIa/b clinical trial under a collaborative agreement with pharmaceutical partner for the treatment of Acute Myocardial Infarction using allogeneic ischemic tolerant human mesenchymal stem cells. The proposed trial will be split into two parts, a Phase IIa and Phase IIb. The Company has already received an IND for the Phase IIa portion of the trial, which will commence before the disbursement of funds by CIRM, in Q4 2013. In Phase IIa 50 patients will be treated at 4 sites, and take approximately 2 years to complete. Following the completion of the Phase IIa portion of the trial, the Company will file for an expanded IND to proceed to the Phase IIb portion of the trial which will treat up to 100 patients and take approximately 2 years to complete. The budget for the project will be approximately $18.7 million over 4 years, $9.35 million to be provided by the Company and its collaborative partner and $9.35 million from CIRM. The proposed therapeutic will advance treatment of AMI by allowing for a post-stent treatment option that may be able to improve the ejection fraction of a damaged heart, decrease the size of the scar resulting from AMI and, as a result, better long-term clinical outcomes. By conducting a Phase II clinical trial, assuming positive results, the Company will be able to move on to a pivotal Phase III trial which could lead to the eventual approval of ischemic tolerant mesenchymal stem cells as a market approved treatment option for post-stent AMI patients. An additional, non-surgical, non-invasive treatment option for AMI could lead to a decrease in the overall direct and indirect costs of AMI, as well as the possibility of a significant increase in quality of life for such patients.
Statement of Benefit to California:
Our proposed clinical trial will have at least one clinical site in the State of California. This will provide an economic influx of at least five million USD ($5M) into the general state economy, whether through salaries, benefits, contractor services, etc. The full funding of this clinical trial will result in the hiring of up to five additional employees. Furthermore, the treatment is intended to improve quality of life for treated patients, increase economic activity by having an increased ability to perform societally useful work by patients who might otherwise receive disability or be unable to work. Approximately six percent (6%) of California’s population has some form of heart disease, making this project of great benefit to a large group of Californians. Additionally, the completion of a successful Phase II clinical trial for ischemic tolerant mesenchymal stem cells will vastly increase the market value of our company. It will also lead to a much larger Phase III clinical trial, funded by a large pharmaceutical company, most of which will be conducted in California. By providing data that shows the efficacy for MSC treatment of AMI, We stand ready to increase acceptance of California’s nascent, but large, stem cell industry as a possible treatment for AMI, as well as other ischemic conditions. Having a definitive FDA approved Phase II clinical trial completed would further the goal of having an approved allogeneic stem cell treatment, which could very well lead to an economic boom in the California regenerative medicine industry in concert with leading regenerative medicine institutions California-wide.
Executive Summary This application describes development of a candidate allogeneic human mesenchymal stem cell (MSC) product for treatment of acute myocardial infarction (AMI). The proposal includes the manufacture of the MSC product, and Phase 2a and Phase 2b clinical trials to assess the safety and preliminary clinical efficacy of the cells. Significance and Impact - While there is unmet medical need for effective treatment after AMI, reviewers noted that this is a competitive area of development and other MSC-based therapeutics are under assessment in Phase 2 and Phase 3 clinical trials for AMI. - The Target Product Profile (TPP) was not well developed and did not adequately reflect the increased availability of current interventional standard of care practices. Reviewers commented that the clinical endpoints and surrogate markers proposed in the TPP would not likely support initiation of Phase 3 clinical trials. - Some reviewers thought that the intended route of administration could confer a competitive advantage over other cellular therapeutics currently under development for AMI. Scientific Rationale and Risk/Benefit - The intended clinical product has been delivered to patients and the applicants report that it has been well tolerated; reviewers interpreted this as suggestive of a manageable risk profile. However, given the results of similar clinical trials in AMI, reviewers also expressed a low expectation for impactful clinical benefit from the proposed therapy. - The scientific rationale behind the product is reasonable and consistent with putative effects of other MSC-based therapeutics. However, insufficient data were presented to support the applicant’s proposal that the candidate MSC product would have increased biological activity compared to other MSC products. - Limited efficacy data with the intended product in cardiac indications were presented and appear to be unpublished. Therapeutic Development Readiness - The applicant has an IND in place to support initiation of the proposed Phase 2a clinical trial. Design and Feasibility - Reviewers predicted that enrollment challenges would make it highly unlikely that the proposed clinical studies could be completed within the 4-year project plan timeline. - Reviewers expressed that the modest clinical efficacy criteria and surrogate markers proposed for the therapy would likely not be sufficient or provide approvable endpoints to support late stage development of the MSC product. - Reviewers commented that the manufacturing plan was feasible, but noted that plans were not included for assay development and validation that would be required for further clinical development of the MSC product. - Reviewers stated that insufficient data were presented in the application to allow an adequate assessment of the MSC product characterization. - The clinical operations plans presented were minimal and lacked detailed risk mitigation strategies. Principal Investigator (PI), Development Team and Leadership Plan - Although the PI does not have a background in cardiovascular medicine, the leadership team has successfully brought their product into the clinic in a variety of therapeutic indications. - The clinical investigators are well experienced in the area and the clinical teams appear qualified to conduct trials in the AMI patient population. Budget - Funding was requested for activities that, according to the presented project timeline, should be completed prior to the time that funding could be available under this RFA. - The overall budget for the proposed clinical studies appears reasonable, but the reviewers questioned the requested funding for additional preclinical studies. Collaborations, Assets, Resources and Environment - Proposed clinical sites, contract services and collaborations appear appropriately qualified and able to provide necessary resources to support the described activities.
- Joy Cavagnaro